2023
α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis
Ishikawa G, Peng X, McGovern J, Woo S, Perry C, Liu A, Yu S, Ghincea A, Kishchanka A, Fiorini V, Hu B, Sun Y, Sun H, Ryu C, Herzog E. α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2023, 324: l639-l651. PMID: 36648147, PMCID: PMC10110730, DOI: 10.1152/ajplung.00119.2022.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic AgentsAnimalsBleomycinDNA, MitochondrialFibroblastsHumansIdiopathic Pulmonary FibrosisLungMiceSignal TransductionConceptsAdrenergic nerve supplyIdiopathic pulmonary fibrosisΑ1 adrenoreceptorsPulmonary fibrosisNerve supplyCultured normal human lung fibroblastsInnate immune ligandsLung fibrosis modelNormal human lung fibroblastsSmooth muscle actinHuman lung fibroblastsAdrenal resectionAdrenoreceptor antagonismExtracellular mtDNAIPF cohortImproved survivalΑ1-adrenoreceptor antagonistsLung fibrosisAdrenal sourceFibroblast accumulationAdrenoreceptor antagonistBleomycin modelFibrosis modelLung fibrogenesisMouse model
2019
Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insights
2017
Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis
Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G. Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480oc.Peer-Reviewed Original ResearchMeSH KeywordsAgedDisease-Free SurvivalDNA, MitochondrialFemaleFibroblastsHumansIdiopathic Pulmonary FibrosisMaleConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsExtracellular mitochondrial DNABronchoalveolar lavageIPF fibroblastsPulmonary fibrosisInnate immune ligandsEvent-free survivalSmooth muscle actin expressionMtDNA concentrationsSmooth muscle actin-expressing myofibroblastsGrowth factor-β1Muscle actin expressionHuman lung fibroblastsTGF-β1 stimulationExtracellular mtDNAIPF cohortClinical outcomesControl subjectsDisease progressionGlycolytic reprogrammingSoluble mediatorsTGF-β1Factor-β1Immune ligands